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Multi-walled carbon nanotubes act as a chemokine and recruit macrophages by activating the PLC/IP3/CRAC channel signaling pathway

The impact of nanomaterials on immune cells is gaining attention but is not well documented. Here, we report a novel stimulating effect of carboxylated multi-walled carbon nanotubes (c-MWCNTs) on the migration of macrophages and uncover the underlying mechanisms, especially the upstream signaling, u...

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Autores principales: Li, Hui, Tan, Xiao-Qiu, Yan, Li, Zeng, Bo, Meng, Jie, Xu, Hai-Yan, Cao, Ji-Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428205/
https://www.ncbi.nlm.nih.gov/pubmed/28331181
http://dx.doi.org/10.1038/s41598-017-00386-3
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author Li, Hui
Tan, Xiao-Qiu
Yan, Li
Zeng, Bo
Meng, Jie
Xu, Hai-Yan
Cao, Ji-Min
author_facet Li, Hui
Tan, Xiao-Qiu
Yan, Li
Zeng, Bo
Meng, Jie
Xu, Hai-Yan
Cao, Ji-Min
author_sort Li, Hui
collection PubMed
description The impact of nanomaterials on immune cells is gaining attention but is not well documented. Here, we report a novel stimulating effect of carboxylated multi-walled carbon nanotubes (c-MWCNTs) on the migration of macrophages and uncover the underlying mechanisms, especially the upstream signaling, using a series of techniques including transwell migration assay, patch clamp, ELISA and confocal microscopy. c-MWCNTs dramatically stimulated the migration of RAW264.7 macrophages when endocytosed, and this effect was abolished by inhibiting phospholipase C (PLC) with U-73122, antagonizing the IP3 receptor with 2-APB, and blocking calcium release-activated calcium (CRAC) channels with SK&F96365. c-MWCNTs directly activated PLC and increased the IP3 level and [Ca(2+)](i) level in RAW264.7 cells, promoted the translocation of the ER-resident stromal interaction molecule 1 (STIM1) towards the membranous calcium release-activated calcium channel modulator 1 (Orai1), and increased CRAC current densities in both RAW264.7 cells and HEK293 cells stably expressing the CRAC channel subunits Orai1 and STIM1. c-MWCNTs also induced dramatic spatial polarization of KCa3.1 channels in the RAW264.7 cells. We conclude that c-MWCNT is an activator of PLC and strongly recruits macrophages via the PLC/IP3/CRAC channel signaling cascade. These novel findings may provide a fundamental basis for the impact of MWCNTs on the immune system.
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spelling pubmed-54282052017-05-15 Multi-walled carbon nanotubes act as a chemokine and recruit macrophages by activating the PLC/IP3/CRAC channel signaling pathway Li, Hui Tan, Xiao-Qiu Yan, Li Zeng, Bo Meng, Jie Xu, Hai-Yan Cao, Ji-Min Sci Rep Article The impact of nanomaterials on immune cells is gaining attention but is not well documented. Here, we report a novel stimulating effect of carboxylated multi-walled carbon nanotubes (c-MWCNTs) on the migration of macrophages and uncover the underlying mechanisms, especially the upstream signaling, using a series of techniques including transwell migration assay, patch clamp, ELISA and confocal microscopy. c-MWCNTs dramatically stimulated the migration of RAW264.7 macrophages when endocytosed, and this effect was abolished by inhibiting phospholipase C (PLC) with U-73122, antagonizing the IP3 receptor with 2-APB, and blocking calcium release-activated calcium (CRAC) channels with SK&F96365. c-MWCNTs directly activated PLC and increased the IP3 level and [Ca(2+)](i) level in RAW264.7 cells, promoted the translocation of the ER-resident stromal interaction molecule 1 (STIM1) towards the membranous calcium release-activated calcium channel modulator 1 (Orai1), and increased CRAC current densities in both RAW264.7 cells and HEK293 cells stably expressing the CRAC channel subunits Orai1 and STIM1. c-MWCNTs also induced dramatic spatial polarization of KCa3.1 channels in the RAW264.7 cells. We conclude that c-MWCNT is an activator of PLC and strongly recruits macrophages via the PLC/IP3/CRAC channel signaling cascade. These novel findings may provide a fundamental basis for the impact of MWCNTs on the immune system. Nature Publishing Group UK 2017-03-22 /pmc/articles/PMC5428205/ /pubmed/28331181 http://dx.doi.org/10.1038/s41598-017-00386-3 Text en © The Author(s) 2017 This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Li, Hui
Tan, Xiao-Qiu
Yan, Li
Zeng, Bo
Meng, Jie
Xu, Hai-Yan
Cao, Ji-Min
Multi-walled carbon nanotubes act as a chemokine and recruit macrophages by activating the PLC/IP3/CRAC channel signaling pathway
title Multi-walled carbon nanotubes act as a chemokine and recruit macrophages by activating the PLC/IP3/CRAC channel signaling pathway
title_full Multi-walled carbon nanotubes act as a chemokine and recruit macrophages by activating the PLC/IP3/CRAC channel signaling pathway
title_fullStr Multi-walled carbon nanotubes act as a chemokine and recruit macrophages by activating the PLC/IP3/CRAC channel signaling pathway
title_full_unstemmed Multi-walled carbon nanotubes act as a chemokine and recruit macrophages by activating the PLC/IP3/CRAC channel signaling pathway
title_short Multi-walled carbon nanotubes act as a chemokine and recruit macrophages by activating the PLC/IP3/CRAC channel signaling pathway
title_sort multi-walled carbon nanotubes act as a chemokine and recruit macrophages by activating the plc/ip3/crac channel signaling pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5428205/
https://www.ncbi.nlm.nih.gov/pubmed/28331181
http://dx.doi.org/10.1038/s41598-017-00386-3
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